Abstract
The major postsynaptic receptor for the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is a complex protein containing a chloride channel and modulatory sites for two classes of drugs, the benzodiazepines (BZ) and anti-convulsants/barbiturates (Olsen, 1982). These GABA receptors are also defined by sensitivity to the agonist muscimol and the antagonist bicuculline (Enna, 1983). Barbiturates and related depressants like pyrazolopyridines that enhance GABA-activated chloride permeability at the tissue and cellular level (Nicoll and colleagues, this volume) also are able to enhance benzodiazepine and GABA receptor binding at the molecular level (Leeb-Lundberg et al., 1980, 1981; Olsen & Snowman, 1982; Wong et al., 1984b). These in vitro barbiturate interactions are dependent on the presence of physiological levels of chloride or other anions able to permeate GABA ion channels, and are blocked by picrotoxin and related chloride channel antagonists, as well as by bicuculline, a GABA receptor antagonist.
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References
ASANO, T. & OGASAWARA, N. (1981). Chloridedependent stimulation of GABA and benzodiazepine receptor binding by pentobarbital. Brain Res., 225, 212–216.
ASANO, T., YAMADA, Y. & OGASAWARA, N. (1983). Characterization of the solubilized GABA and benzodiazepine receptor from various regions of bovine brain. J. Neurochem., 40, 209–214.
BARKER, J.C., GRATZ, E., OWEN, D.G. & STUDY, R.E. (1984). Pharmacological effects of clinically important drugs on the excitability of cultured mouse spinal neurons. In Actions and Interactions of GABA and Benzodiazepines. Bowery, N.G. (ed.) pp.203–216, New York: Raven Press.
BRADFORD, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248–252.
ENNA, S.J. (ed.) (1983). The GABA Receptors, Clifton, New Jersey: Humana Press.
FROEHNER, S.C., REINESS, C.T. & HALL, Z.W. (1977). Subunit structure of the acetylcholine receptor from denervated rat skeletal muscle. J. biol. Chem., 252, 8589–8594.
GAVISH, M. & SNYDER, S.H. (1981). λ-Aminobutyric acid and benzodiazepine receptors: copurification and characterization. Proc. natn. Acad. Sci. U.S.A., 78, 1939–1942.
GREENLEE, D.V. & OLSEN, R.W. (1979). Solubilization of GABA receptor protein from mammalian brain. Biochem. biophys. Res. Commun., 88, 380–387.
HARRISON, N.L. & SIMMONDS, M.A. (1983). Two distinct interactions of barbiturates and chlormethiazole with the GABA receptor complex in rat cuneate nucleus in vitro. Br. J. Pharmac., 80, 387–394.
HUANG, L.Y. & BARKER, J.L. (1980). Pentobarbital: stereospecific actions of the (+) and (−) isomers
revealed on cultured mammalian neurons. Science, 207, 195–197.
KING, R.G. & OLSEN, R.W. (1984). Solubilization of convulsant/barbiturate binding activity on the GABA/benzodiazepine receptor complex. Biochem. biophys. Res. Commun., 119, 530–536.
KNABE, V.J., RUMMEL, W., BUCH, H.P. & FRANZ, N. (1978). Optisch aktive Barbiturate. Synthese, Konfiguration and pharmacologische wirkung. Arzneimittel-Forschung, 28, 1048–1056.
LEEB-LUNDBERG, F. & OLSEN, R.W. (1982). Interactions of barbiturates of various pharmacological categories with benzodiazepine receptors. Mol. Pharmac., 21, 320–328.
LEEB-LUNDBERG, F., SNOWMAN, A. & OLSEN, R.W. (1980). Barbiturate receptors are coupled to benzodiazepine receptors. Proc. natn. Acad. Sci. U.S.A., 77, 7468–7472.
LEEB-LUNDBERG, F., SNOWMAN, A. & OLSEN, R.W. (1981). Perturbation of benzodiazepine receptor binding by pyrazolopyridines involves picrotoxinin/barbiturate receptor sites. J. Neurosci., 1, 471–477.
MACDONALD, R.L. & BARKER, J.L. (1978). Different actions of anticonvulsant and anesthetic barbiturates revealed by use of cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res., 167, 323–326.
MOHLER, H. & OKADA, T. (1977). Benzodiazepine receptors: demonstration in the central nervous system. Science, 198, 849–851.
MÖHLER, H., BATTERSBY, M.K. & RICHARDS, J.C. (1980). Benzodiazepine receptor protein identified and visualized in brain tissue by a photoaffinity label. Proc. natn. Acad. Sci. U.S.A., 77, 1666–1670.
NICOLL, R.A., ECCLES, J.C., OSHIMA, T.C. & RUBIA, F. (1975). Prolongation of hippocampal inhibitory postsynaptic potentials by barbiturates. Nature, 258, 625–627.
OLSEN, R.W. (1982). Drug interactions at the GABA receptor ionophore complex. A. Rev. Pharmac. Toxicol., 22, 245–277.
OLSEN, R. W., BERGMAN, M.O., VAN NESS, P.C., LUMMIS, S.C., WATKINS, A.E., NAPIAS, C. & GREENLEE, D.V. (1981). γ-Aminobutyric acid receptor binding in mammalian brain: heterogeneity of binding sites. Mol. Pharmac., 19, 217–227.
OLSEN, R.W. & SNOWMAN, A.M. (1982). Chloride-dependent enhancement by barbiturates of GABA receptor binding. J. Neurosci., 2, 1812–1823.
OLSEN, R.W. & SNOWMAN, A.M. (1983). [3H]Bicuculline methochloride binding to low affinity GABA receptor sites. J. Neurochem., 41. 1563–1663.
OLSEN, R.W., FISCHER, J.B. & DUNWIDDIE, T.V. (1984a). Barbiturate enhancement of λ-aminobutyric acid receptor binding and function as a mechanism of anesthesia. In Molecular Mechanisms of Anaesthesia. Roth, S. & Miller, K. (eds) (in press).
OLSEN, R.W., SNOWHILL, E.W. & WAMSLEY, J.K. (1984b). Autoradiographic localization of low affinity GABA receptors with [3H]bicuculline methochloride. Eur. J. Pharmac., 99, 247–248.
OLSEN, R.W., WONG, E.H.F., STAUBER, G.B., MURAKAMI, D., KING, R.G. & FISCHER, J.B. (1984c). Biochemical Properties of the GABA/Barbiturate/Benzodiazepine Receptor-Chloride Ion Channel Complex. In Neurotransmitter Receptors: Mechanisms of Action and Regulation. Kito, S., Segawa, T., Kuriyarna, K., Yamamura, H.I. & Olsen, R.W. (eds) pp.205–219, New York: Plenum Press.
SIGEL, E. & BARNARD, E.A. (1984). A λ-aminobutyric acid/benzodiazepine receptor complex from bovine cerebral cortex. Improved purification with preservation of regulatory sites and their interactions. J. biol. Chem., 259, 7219–7223.
SIMMONDS, M.A. (1981). Distinction between the effects of barbiturates, benzodiazepines and phenytoin on responses to γ-aminobutyric acid receptor activation and antagonism by bicuculline and picrotoxinin. Br. J. Pharmac., 73, 739–747.
SQUIRES, R.F. & BRAESTRUP, C. (1977). Benzodiazepine receptors in rat brain. Nature, 266, 732–734.
SQUIRES, R.F., CASIDA, J.E., RICHARDSON, M. & SAEDERUP, E. (1983). [35S]t-Butyl-bicyclophosphorothionate binds with high affinity to brain-specific sites coupled to γ-aminobutyric acid-A and ion recognition sites. Mol. Pharmac., 23, 326–336.
STEPHENSON, F.A. & OLSEN, R.W. (1982). Solubilization by CHAPS detergent of barbiturate-enhanced benzodiazepine-GABA receptor complex. J. Neurochem., 39, 1579–1586.
STEPHENSON, F.A., WATKINS, A.E. & OLSEN, R.W. (1982). Physicochemical characterization of detergent-solubilized γ-aminobutyric acid and benzodiazepine receptor protein from bovine brain. Eur. J. Biochem., 123, 291–298.
SUPAVILAI, P. & KAROBATH, M. (1979). Stimulation of benzodiazepine receptor binding by SQ 20009 is chloride-dependent and picrotoxin-sensitive. Eur. J. Pharmac., 60, 111–113.
SUPAVILAI, P., MANNONEN, A. & KAROBATH, M. (1982). Modulation of GABA binding sites by CNS depressants and CNS convulsants. Neurochem. Int., 4, 259–268.
TALLMAN, J.F., PAUL, S.M., SKOLNICK, P. & GALLAGER, D.W. (1980). Receptors for the age of anxiety: pharmacology of the benzodiazepines. Science, 207, 274–281.
TICKU, M.K., BAN, M. & OLSEN, R.W. (1978). Binding of [3H]α-dihydropicrotoxinin, a γ-aminobutyric acid synaptic antagonist, to rat brain membranes. Mol. Pharmac., 14, 391–402.
TICKU, M.K. & MAKSAY, G. (1983). Convulsant/depressant site of action at the allosteric benzodiazepine-GABA receptor-ionophore complex. Life Sci., 33, 2263–2375.
TICKU, M.K. & OLSEN, R.W. (1978). Interaction ot barbiturates with dihydropicrotoxin in binding sites related to the GABA receptor-ionophore system. Life Sci., 22, 1643–1651.
WHITTLE, S.R. & TURNER, A.J. (1982). Differential effects of sedative and anticonvulsant barbiturates on specific [3H]GABA binding to membrane preparations from rat brain cortex. Biochem. Pharmac., 31, 2891–2895.
WILLOW, M. & JOHNSTON, G.A.R. (1980). Enhancement of GABA binding by pentobarbitone. Neurosci. Lett., 18, 323–327.
WONG, E.H.F., LEEB-LUNDBERG, L.M.F., TEICHBERG, V.I. & OLSEN, R.W. (1984a). γ-Aminobutyric acid activation of 36Cl− flux in rat hippocampal slices and its potentiation by barbiturates. Brain Res., 303, 267–275.
WONG, E.H.F., SNOWMAN, A.M., LEEB-LUNDBERG, L.M.F. & OLSEN, R.W. (1984b). Barbiturates inhibit GABA antagonist and benzodiazepine inverse agonist binding. Eur. J. Phanmac. (in press).
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Olsen, R.W., Fischer, J.B., Stauber, G.B., King, R.G., Yang-Ransom, J. (1984). Purification and properties of the GABA/benzodiazepine/barbiturate receptor protein from rat brain. In: Paton, W., Mitchell, J., Turner, P., Padgham, C., Ashcroft, E. (eds) IUPHAR 9th International Congress of Pharmacology London 1984. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-17615-1_25
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